The ultimate aim of this project is to define CJD agent specific (non-host) molecules, i.e. proteins and nucleic acids. It is obvious that definition of these elements will be invaluable for the ultimate understanding of these agents and the dementias they induce. The identification of truly agent specific molecules will also permit reliable diagnostic tests for human dementias. The project is split into two parts. The first deals with a definitive evaluation of the size and density of the infectious agent and will be useful for further systematic purification of agent, and detection of agent protein(s). The second part concentrates on detection, amplification and sequencing of specific RNAs (cDNA clones) that may belong to the infectious agent.